Since flavonoids have an anti-oxidation effect, the flavonoids have been used in prevention of deterioration for flavor of foods, prevention of fading of color and the like, and lists of foods additives, already existing additives and antioxidants of Japan have reported numerous substances containing flavonoids as an active ingredient such as catechins, enzymatically modified rutins, rutin extracts, tea extracts, Chinese bayberry extracts. In addition, as physiological actions of flavonoids, anti-tumor, lowering of cholesterols, lowering of blood pressure, lowering of blood sugars, reduction in body fats and the like have been reported, and flavonoids have been widely used in medicaments, foodstuff, health foods, foods for specified health use, cosmetics, and the like.
Flavonoids are contained in vegetables, fruits, teas and the like, and 3,000 or more kinds of flavonoids have been known, but many of flavonoids are sparingly soluble in water, so that it is difficult to use flavonoids for foods, beverages, medicaments or cosmetics that would require readily water-soluble ability, as in refreshing beverages, aqueous agents and the like. For example, a solubility of hesperidin or rutin which is a representative flavonoid is 0.01% or less, so that it is difficult to use it for refreshing beverages, cosmetic lotions or the like.
Sparingly soluble flavonoids can be classified to ones having a rhamnoside structure and ones without a rhamnoside structure, and it has been reported that isoquercitrin, hesperetin-7-glucoside, naringenin, or naringenin-7-glucoside in which rhamnose is cleaved has higher bioavailability in rats than rutin, hesperidin, or naringin having a rhamnoside structure (Non-Patent Publications 1 to 3).
In addition, it has been known that bioavailability is improved and physiological effects are effectively shown by including a sparingly soluble flavonoid with a cyclodextrin or subjecting a sparingly soluble flavonoid to glycosidation. As to an inclusion compound, for example, it has been reported that an isoquercitrin (1 M)-γ-cyclodextrin (5 M) inclusion compound has a higher body absorption rate than isoquercitrin (Patent Publication 1), that in an experimentation with mice, a hesperetin-β-cyclodextrin inclusion compound or the like has higher bioavailability (AUC: 0 to 9 hours), and higher effects of allergic reaction-suppressing actions, bloodstream-improving actions, and sensitivity to cold-improving actions than hesperetin (Patent Publication 2), and that a naringenin-hydroxypropyl β-cyclodextrin inclusion compound has an elevated bioavailability (rat), a reduced VLDL (very low lipoprotein), and an increased rate of glucose clearance as compared to naringenin (Non-Patent Publication 4). As to glycosidation, for example, it has been reported that anti-allergic effects by mice are in the order of “enzymatically modified rutin<isoquercitrin<enzymatically modified isoquercitrin,” and an enzymatically modified isoquercitrin in which a rhamnose is removed and which is water-soluble shows highest effects (Non-Patent Publication 5).
In addition to the above publications, a method for cleaving a rhamnose from a sparingly soluble flavonoid having a rhamnoside structure has been disclosed in, for example, Patent Publications 3 to 6. A method for including a sparingly soluble flavonoid with a cyclodextrin has been disclosed in, for example, Patent Publications 2, 7 and 8. A method for subjecting a sparingly soluble flavonoid to glycosidation has been disclosed in, for example, Patent Publications 9 and 10. Additionally, Patent Publication 11 discloses a method for solubilization including allowing a sparingly soluble flavonoid to be copresent with a soybean saponin and/or a composition of glycosides of malonyl isoflavone as a method for making a sparingly soluble flavonoid readily water-soluble.
In addition, a method for improving water solubility characterized by combining a sparingly soluble flavonoid with readily water-soluble flavonoid glycosides as a method for improving a solubility of a sparingly soluble flavonoid (Patent Publications 3 to 4 and 12), and a water-soluble flavonoid characterized in that the flavonoid contains a sparingly soluble flavonoid-β-cyclodextrin and a glycosyl hesperidin (Patent Publication 8) have been disclosed.